This Sexually Transmitted Infections (STI) Cooperative Research Center application from the University of Alabama at Birmingham is comprised of three innovative, multidisciplinary translational research projects addressing the microbial origins and pathogenesis of the most prevalent genital discharge syndromes in men (non-gonococcal urethritis [NGU]) and women (bacterial vaginosis [BV]), as well as interactions of these syndromes with the most prevalent curable bacterial STI, Chlamydia trachomatis (CT). Thus, we named the proposal the Discharge Syndrome Concordance and Interactions Study (DiSCIS). Our group of highly productive, established investigators will work together to conduct 3 projects to evaluate patients from a unique cohort of sexual partners: men with (cases) or without (controls) symptomatic NGU and their female partners. We will use cutting edge microbiological and molecular science tools, and rely on integrated clinical, laboratory, and biostatistics/bioinformatics core services. The goal of Project 1 is to advance understanding of the concordance of known STI pathogens and genital microbiome composition within sexual partnerships (dyads) and the effect of treatment on the microbiome and signs and symptoms of infection. Project 1 hypotheses are: 1) concordance among known STIs is associated with inflammation (NGU), 2) there will be more concordance in microbial community composition within partnerships among those without NGU and following treatment among those with NGU and 3) that certain organisms (Ureaplasma parvum) or microbiome characteristics may help protect from mucosal infection/inflammation. The goal of Project 2 is to advance knowledge of BV pathogenesis through comprehensive evaluation of Gardnerella vaginalis (GV) virulence factors that contribute to infection of vaginal epithelial cells and progression to BV and also to determine classification schema for grouping virulent and avirulent GV strains into distinct clades. The main Project 2 hypothesis is that specific GV virulence factors are associated with BV development. The goal of Project 3 is to advance understanding of the influence of Trichomonas vaginalis (TV) infection and/or BV on CT infection concordance within sexual dyads and the effect of these concomitant infections on CT clearance after treatment and risk for CT infection persistence and/or recurrence. The main Project 3 hypothesis is that CT concordance rates are higher and CT clearance duration longer after therapy in the presence of these concomitant infections. As described in detail in the DiSCIS Overview, the projects are highly complementary and provide substantial value added when performed from the same cohort. Further, a data and specimen repository will be created from these projects that will serve as a powerful resource for future STI studies. DiSCIS findings will provide new knowledge on the pathogenesis of microbes contributing to NGU and BV, and the influence of TV infection and/or BV on CT concordance and outcomes. The long-term goal of the research is to translate findings into improved or new strategies for STI prevention, diagnosis, and/or management.